P350: BLINATUMOMAB AND DONOR LYMPHOCYTE INFUSION (DLI) FOR MOLECULAR RELAPSE AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PEDIATRIC PATIENTS
Authors: F. Muriano, F. Cacace, V. Caprioli, M. R. D’amico, G. De Simone, G. Giagnuolo, G. Menna, F. P. Tambaro
Journal: HemaSphere (2022)

Background: Detection of measurable residual disease (MRD) after Hematopoietic Stem Cell Transplantation (HSCT) is an early predictor of frank relapse. The role of DLI as a pre-emptive treatment to prevent relapse is still debated. Blinatumomab, a CD3/CD19 bispecific T-cell engager molecule, is approved in adult patients with MRD and in children with relapsed or refractory acute lymphoblastic leukemia (ALL). Aims: We evaluated the safety and feasibility of blinatumomab plus DLI to treat MRD-positive pediatricALLafter HSCT. Here, we report our experience of three patients with post-transplant MRD-positive ALL who received blinatumomab and DLI. Methods: Three pediatric patients with high-risk B-ALLwere treated according to AEIOP ALL 2009 and AIEOP ALL 2017 protocols and referred for allo-HSCT. Patients became MRD-positive after allo-HSCT and received blinatumomab with DLI.Patients' characteristics are summarized in the Table. Results: Patient 1 developed CNS relapse during maintenance, then received salvage therapy according to the INTREALL HR 2010 and 1 course of blinatumomab, achieving MRD-positive CR1.Patient 2, a 16-year old female, had secondary ALL and achieved CR1 after 1 course of chemotherapy and subsequently received 2 courses of blinatumomab, due to chemotherapy-associated toxicity and achieved MRD-undetectable CR1. Patient 3, a 17-year old male was primary refractory to 2 lines of chemotherapy and blinatumomab, received 2 courses of inotuzumab and achieved an MRD-positive complete remission (CR).All patients proceeded to allo-SCT and were MRD-positive at 8, 31 and 14 weeks post-allo-SCT, respectively. All patients discontinued immunosuppressive therapy and received 2, 1 and 4 courses of DLI with blinatumomab, respectively. Blinatumomab was started one week after each DLI, was given at a dose of 15-28cg/kg for a total of 4 weeks each course. Only patient 3 experienced Grade 2 liver GVHD. None of the patients experienced serious adverse events requiring blinatumomab discontinuation. Patient 3 developed isolated CNS relapse after 4 courses of combined DLI plus blinatumomab; patient 2 achieved and remains in MRD-undetectable CR with current follow up and a patient 1 achieved MRD-negative CR after two courses of combined treatment and CNS relapse. Image:Summary/Conclusion: The role of cellular therapy with DLI is still debated in ALL. Most post-transplant relapses are associated withloss of surface HLA bythe leukemia cells, hence DLI alone has limited efficacy in patients with post HSCT relapse. Blinatumomab directs T cells to bind CD19 present on malignant B cells and engages CD3 on T cells causing activation and inducing cytotoxicity against ALL blasts. We, therefore, tested the efficacy of blinatumomab plus DLI in 3 MRD-positive patients with ALL after allogeneic HSCT. The use of blinatumomab allowed recruitment of fit donor-derived T lymphocytes (not exposed to immune suppressive agents) against ALL B cells. This hypothesis is supported by the fact thatpatient 3, who received blinatumomab pre-HSCT and had disease progression, probably due to lack of T cells showed by flow cytometry, achieved MRD-undetectablestatus after receiving DLI plus blinatumomab post-transplant. Twopatients reached stable MRD-undetectablestatusand 2 subsequently developed CNS relapse; none received CNS prophylaxis post-HSCT. We hypothesize that blinatumomab plus DLI can clear the hematologic disease, but it is not effective in preventing CNS relapse. Although very interesting, this hypothesis should be confirmed in a larger number of patients.